USP54 is a potential therapeutic target in castration-resistant prostate cancer
Abstract Background USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. Methods We esta...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Urology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12894-024-01418-7 |
| _version_ | 1797273085461659648 |
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| author | Cheng Zhou Xuehu Zhang Hangbin Ma Yinghao Zhou Yibo Meng Chenchen Chen Guowei Shi Wandong Yu Jun Zhang |
| author_facet | Cheng Zhou Xuehu Zhang Hangbin Ma Yinghao Zhou Yibo Meng Chenchen Chen Guowei Shi Wandong Yu Jun Zhang |
| author_sort | Cheng Zhou |
| collection | DOAJ |
| description | Abstract Background USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. Methods We established the CRPC LNCaP-AI cell line from the hormone-sensitive prostate cancer (HSPC) LNCaP cell line. RNA-Seq was utilized to explore DUB expression levels in LNCaP and LNCaP-AI. USP54 was knocked down, and its effects on cell growth were evaluated in vitro and in vivo. Bioinformatics analyses were conducted to explore signaling pathways affected by USP54 in PCa. Quantitative polymerase chain reaction was used to confirm key signaling pathways involved. Results USP54 was the most strongly upregulated DUB in LNCaP-AI cells compared with LNCaP cells. USP54 levels were higher in PCa than in normal tissues. USP54 silencing suppressed the proliferation of PCa cell lines, both in vitro and in vivo. USP54 expression was positively correlated with the androgen receptor (AR) signaling level in PCa samples, and USP54 knockdown inhibited AR signaling in PCa cells. Conclusions USP54 was upregulated during HSPC progression to CRPC. USP54 depletion suppressed CRPC cell proliferation both in vitro and in vivo. USP54 may facilitate PCa progression by regulating AR signaling. |
| first_indexed | 2024-03-07T14:38:32Z |
| format | Article |
| id | doaj.art-1ef892c83f4e4c48ab2f7cda93033182 |
| institution | Directory Open Access Journal |
| issn | 1471-2490 |
| language | English |
| last_indexed | 2024-03-07T14:38:32Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Urology |
| spelling | doaj.art-1ef892c83f4e4c48ab2f7cda930331822024-03-05T20:28:42ZengBMCBMC Urology1471-24902024-02-0124111110.1186/s12894-024-01418-7USP54 is a potential therapeutic target in castration-resistant prostate cancerCheng Zhou0Xuehu Zhang1Hangbin Ma2Yinghao Zhou3Yibo Meng4Chenchen Chen5Guowei Shi6Wandong Yu7Jun Zhang8Department of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityDepartment of Urology, Shanghai Fifth People’s Hospital, Fudan UniversityAbstract Background USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. Methods We established the CRPC LNCaP-AI cell line from the hormone-sensitive prostate cancer (HSPC) LNCaP cell line. RNA-Seq was utilized to explore DUB expression levels in LNCaP and LNCaP-AI. USP54 was knocked down, and its effects on cell growth were evaluated in vitro and in vivo. Bioinformatics analyses were conducted to explore signaling pathways affected by USP54 in PCa. Quantitative polymerase chain reaction was used to confirm key signaling pathways involved. Results USP54 was the most strongly upregulated DUB in LNCaP-AI cells compared with LNCaP cells. USP54 levels were higher in PCa than in normal tissues. USP54 silencing suppressed the proliferation of PCa cell lines, both in vitro and in vivo. USP54 expression was positively correlated with the androgen receptor (AR) signaling level in PCa samples, and USP54 knockdown inhibited AR signaling in PCa cells. Conclusions USP54 was upregulated during HSPC progression to CRPC. USP54 depletion suppressed CRPC cell proliferation both in vitro and in vivo. USP54 may facilitate PCa progression by regulating AR signaling.https://doi.org/10.1186/s12894-024-01418-7USP54Prostate cancerDeubiquitinaseCRPC |
| spellingShingle | Cheng Zhou Xuehu Zhang Hangbin Ma Yinghao Zhou Yibo Meng Chenchen Chen Guowei Shi Wandong Yu Jun Zhang USP54 is a potential therapeutic target in castration-resistant prostate cancer BMC Urology USP54 Prostate cancer Deubiquitinase CRPC |
| title | USP54 is a potential therapeutic target in castration-resistant prostate cancer |
| title_full | USP54 is a potential therapeutic target in castration-resistant prostate cancer |
| title_fullStr | USP54 is a potential therapeutic target in castration-resistant prostate cancer |
| title_full_unstemmed | USP54 is a potential therapeutic target in castration-resistant prostate cancer |
| title_short | USP54 is a potential therapeutic target in castration-resistant prostate cancer |
| title_sort | usp54 is a potential therapeutic target in castration resistant prostate cancer |
| topic | USP54 Prostate cancer Deubiquitinase CRPC |
| url | https://doi.org/10.1186/s12894-024-01418-7 |
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